Encoded design integrated synthesis of nucleic acids, and phospholipids, and related pharmaceutical products

Abstract

Provided herein are reactive aromatic molecules (e.g., substituted chrysene heterodimers) encodable as base-four sequences for the design and integrated synthesis of nucleic acids (e.g., DNA, RNA, hybrid DNA/RNA) and associated phospholipid bilayers (e.g., cellular membranes). For example, 3,6,9,12-tetrasubstituted chrysene is coupled with 6,12-disubstituted chrysene through π-electron stacking to form a base-four heterodimer. The orientation of the ring structure of the tetrasubstituted chrysene in this heterodimer comprises a base-two (binary) structure and the relative alignment of the ring structure of the disubstituted chrysene to the tetrasubstituted chrysene comprises a second independent base-two (binary) structure. This collectively results in a base-four (quaternary) complex composed of four independent reaction environments. Methods of forming the heterodimers (and conjugated systems) include coupling sidechains of ethoxylated alcohol by phosphorylation. This may result in phosphodiester linkages at the 6,12 positions and/or uncoupled phosphorylated sidechains of ethoxylated alcohol at the 3,9 positions of the reactive aromatic molecules. The uncoupled phosphorylated sidechains may polymerize with adjacent tetrasubstituted chrysene through phosphodiester linkages. Various methods for initiating a reaction (e.g., oxidative cleavage) within the assembly of these π-electron stacked heterodimers can be utilized to produce nucleic acid sequences from the stacked tetrasubstituted chrysenes along with an associated phospholipid structure from the coupled disubstituted chrysene. Also provided herein are encoding and decoding design relations that can be utilized to map the base-four substituted chrysene heterodimers to the base-four nucleic acids (e.g., DNA, RNA, hybrid DNA/RNA). The present disclosure also includes various methods of regulating the sequence of substituted heterodimers to produce a specific encoding type of nucleic acid (e.g., DNA, RNA, hybrid DNA/RNA) and direct the 5′-3′ polymerization direction. The present disclosure also includes polycyclic pharmaceutical molecular agents resultant from the structural correlations in deriving the base-four heterodimer for subsequent synthesis to a sequence of nucleic acids and phospholipids.

1 . A compound having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         2 . A compound having the structure: 
       
         
           
           
               
               
           
         
         wherein 
         n1 and n2 are independently 0-15; 
         m1 and m2 are independently at each occurrence 0-15; 
         B L  has the structure: 
       
       
         
           
           
               
               
           
         
         I L  has the structure: 
       
       
         
           
           
               
               
           
         
         X 1  has the structure: 
       
       
         
           
           
               
               
           
         
       
       and
 X 2  has the structure: 
 
       
         
           
           
               
               
           
         
         where the wavy bond indicates conjugation to the adjacent moiety; 
         or pharmaceutically acceptable salts thereof. 
       
     
     
         3 . The compound according to  claim 2 , wherein the compound has the structure (I 1 —(C L ) 2 —I 2 ): 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound according to  claim 2 , wherein m1+m2+n1+n2 is less than or equal to 16. 
     
     
         5 . The compound according to  claim 2 , wherein X 1  is 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 2 , wherein m1 is greater than 0. 
     
     
         7 . The compound of  claim 2 , wherein m2 is greater than 0. 
     
     
         8 . The compound of  claim 2 , wherein X 2  is 
       
         
           
           
               
               
           
         
       
     
     
         9 . A compound having the structure: 
       
         
           
           
               
               
           
         
         wherein the wavy bond is the point of conjugation to the adenine of RNA or DNA.